Evaluation of uptake and transport of cationic and anionic ultrasmall iron oxide nanoparticles by human colon cells

Abstract

Blanka Halamoda Kenzaoui1, Maya R Vilà2, Josep M Miquel2, Feride Cengelli1, Lucienne Juillerat-Jeanneret11Centre Hospitalier Universitaire Vaudois (CHUV) and University of Lausanne (UNIL), Lausanne, Switzerland; 2Leitat Technological Center, Barcelona, SpainAbstract: Nanoparticles (NPs) are in clinical use or under development for therapeutic imaging and drug delivery. However, relatively little information exists concerning the uptake and transport of NPs across human colon cell layers, or their potential to invade three-dimensional models of human colon cells that better mimic the tissue structures of normal and tumoral colon. In order to gain such information, the interactions of biocompatible ultrasmall superparamagnetic iron oxide nanoparticles (USPIO NPs) (iron oxide core 9–10 nm) coated with either cationic polyvinylamine (aminoPVA) or anionic oleic acid with human HT-29 and Caco-2 colon cells was determined. The uptake of the cationic USPIO NPs was much higher than the uptake of the anionic USPIO NPs. The intracellular localization of aminoPVA USPIO NPs was confirmed in HT-29 cells by transmission electron microscopy that detected the iron oxide core. AminoPVA USPIO NPs invaded three-dimensional spheroids of both HT-29 and Caco-2 cells, whereas oleic acid-coated USPIO NPs could only invade Caco-2 spheroids. Neither cationic aminoPVA USPIO NPs nor anionic oleic acid-coated USPIO NPs were transported at detectable levels across the tight CacoReady™ intestinal barrier model or the more permeable mucus-secreting CacoGoblet™ model.Keywords: iron oxide nanoparticles, human colon cells, spheroids, transport, gastrointestinal barrier